Advances in the treatment of HIV disease have produced dramatic reductions in AIDS-related morbidity and mortality in the United States and worldwide. In addition to multiple effective drug regimens from 4 licensed drug classes, clinicians have available a range of laboratory techniques, including CD4 cell counts, HIV RNA and resistance tests. Yet these many advances in care have given rise to new challenges, in terms of long-term toxicities, development of resistance, and allocating scarce resources. Over the past decade, our research team has developed a computer simulation of HIV disease: the "Cost-effectiveness of Preventing AIDS Complications" or "CEPAC" model. We have used this model in a rapid response fashion to address a host of important questions at the interface of HIV clinical care and policy in the US. In the last 3 and 1 1/2 years of NIAID support, we have published 21 manuscripts on topics including the impact and cost-effectiveness of antiretroviral therapy (ART), the optimal use of laboratory tests, and the role of HIV testing. In this continuation, we propose to further refine and update the CEPAC model to address several critical emerging questions in HIV management. Our specific aims are: 1) To examine strategies related to timing and sequencing of approved and investigational antiretroviral agents. We will address: a) earlier versus later initiation of therapy;b) clinical strategies for switching therapy accounting for partial virologic suppression;c) the impact of regimens with varying cardiovascular risk profiles;and d) the cost-effectiveness of novel agents and new treatment strategies. 2) To examine issues related to gender and racial/ethnic differences in treatment and access to HIV care in the United States. We will assess: a) clinical guidelines for ART and prophylaxis targeted at women;b) the risks as well as benefits of using efavirenz in women of childbearing age;and c) the impact of incomplete access to care for vulnerable sociodemographic groups. The CEPAC research team has developed an international reputation with a proven record of producing and disseminating findings that have helped set priorities in HIV care, clinical trials, and guideline development. In this proposal, our objective is to continue to exert a major impact on HIV care in the United States over the next 4 years.